IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation

Senra, Luisa; Mylonas, Alessio; Kavanagh, Ruairi D; Fallon, Padraic G; Conrad, Curdin; Borowczyk-Michalowska, Julia; Wrobel, Ludovic; Kaya, Gurkan; Yawalkar, Nikhil; Boehncke, Wolf-Henning; Brembilla, Nicolo

doi:10.1016/j.jid.2019.01.021

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Title		IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation
Authors		Senra, Luisa Mylonas, Alessio Kavanagh, Ruairi D Fallon, Padraic G Conrad, Curdin Borowczyk-Michalowska, Julia Wrobel, Ludovic Kaya, Gurkan Yawalkar, Nikhil Boehncke, Wolf-Henning Brembilla, Nicolo show all authors [1 - 11]
Published in		Journal of investigative dermatology. 2019, vol. 139, no. 8, p. 1732-1742.e17
Abstract		IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be up-regulated in distinct skin inflammatory diseases such as psoriasis and atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here, we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application or tape stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-distributed stochastic neighbor embedding-guided multiparameter flow cytometry analysis, in mice. In humans, IL-17E promotes the recruitment of neutrophils via activation of macrophages in a p38-dependent mechanism. In addition, IL-17E is up-regulated in neutrophil-rich inflammatory skin diseases, such as pyoderma gangrenosum and acute generalized exanthematous pustulosis. Our data show a role for IL-17E in skin inflammation that is unrelated to the development of type 2 immune reactions. We propose that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation.
Keywords		Acute Generalized Exanthematous Pustulosis/immunology/pathology — Adjuvants, Immunologic/administration & dosage — Animals — Dermatitis/immunology/pathology — Disease Models, Animal — Female — Humans — Imiquimod/administration & dosage — Immunity, Innate — Interleukin-17/immunology/metabolism — Interleukins/genetics/immunology/metabolism — Macrophages/immunology/metabolism — Mice — Mice, Knockout — Neutrophils/immunology/metabolism — Pyoderma Gangrenosum/immunology/pathology — Skin/cytology/immunology/pathology — Up-Regulation — p38 Mitogen-Activated Protein Kinases/metabolism
Identifiers		DOI: 10.1016/j.jid.2019.01.021 PMID: 30738055
Full text		Article (Published version) (5 MB) - Limited access to UNIGE Other version: https://www.sciencedirect.com/science/article/pii/S0022202X19301010
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Mécanismes des pathologies de l'inflammation cutanée (919)
Projects		Swiss National Science Foundation: 310030_152680 Swiss National Science Foundation: 310030_175470
Citation (ISO format)		SENRA, Luisa et al. IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation. In: Journal of Investigative Dermatology, 2019, vol. 139, n° 8, p. 1732-1742.e17. doi: 10.1016/j.jid.2019.01.021 https://archive-ouverte.unige.ch/unige:137814